Enantiomerically enriched F2-dihomo-isoprostanes and F3isoprostanes have been synthesized. Such compounds are derived from the action of reactive oxygen species on the phospholipid-bound polyunsaturated fatty acids (PUFA), adrenic acid and eicosapentaenoic acid, respectively. Of special interest are the F2-dihomo-isoprostanes because they could represent potential biomarkers for myelin damage as its main PUFA constituent is adrenic acid. Our strategy, based on a pivotal enantiomerically enriched intermediate, has allowed access to F2-dihomo-IsoP and both C5 epimers of 5-F3t-IsoP for the first time.